Wierzba Thomas F, Bourgis Alexandra
PATH, 455 Massachusetts Ave. NW, Washington, DC 2001-2621, USA.
PATH, 455 Massachusetts Ave. NW, Washington, DC 2001-2621, USA.
Vaccine. 2017 Jan 23;35(4):503-507. doi: 10.1016/j.vaccine.2016.12.006. Epub 2016 Dec 26.
Enterotoxigenic Escherichia coli (ETEC) causes severe acute watery diarrhea. No ETEC vaccine is available but candidates are in development, including ETVAX, an oral, whole-cell inactivated vaccine. ETVAX is being tested in a descending-age trial in Bangladesh. If found safe and immunogenic, investigators may test it for efficacy in children. Like oral rotavirus vaccines, we expect that ETVAX will be most effective at decreasing the incidence of moderate-to-severe ETEC episodes. Thus, for an efficacy trial outcome, it will be necessary to triage patients into moderate-to-severe versus mild disease. A severity scale specific to ETEC does not exist. To develop this scale, PATH convened a committee of international experts for a two-day meeting to strategize on diagnostic scale development. The workshop began with four presentations. The first described existing scales, item selection, and issues related to validation, reliability, and ease of use. The other three presentations provided details on the following published scores: the DHAKA score, validated for use with Bangladeshi children seeking diarrhea treatment; a modified-Vesikari score for evaluating North American outpatient children with diarrhea; and the Community Diarrhea Assessment (CODA) score developed for passive-case surveillance of Peruvian children with diarrhea. Following the presentations and discussion, the committee made several recommendations including: modifying existing scores to make them ETEC-centric; evaluating scoring systems against an objective measure of dehydration (i.e., the percent change in a child's bodyweight following rehydration); and adding an item to the scale measuring ETEC effects on growth faltering. The committee also discussed using available data sets to evaluate scores, but was concerned that if investigators characterized patients using different procedures than prescribed by the score, the results would be difficult to interpret. Committee members suggested new data collection and recommended conducting studies in Sub-Saharan Africa. The study results would be presented for peer-review and to regulatory authorities.
产肠毒素大肠杆菌（ETEC）可导致严重的急性水样腹泻。目前尚无ETEC疫苗，但有几种候选疫苗正在研发中，包括口服全细胞灭活疫苗ETVAX。ETVAX正在孟加拉国进行一项年龄递减试验。如果该疫苗被证明安全且具有免疫原性，研究人员可能会对其在儿童中的疗效进行测试。与口服轮状病毒疫苗一样，我们预计ETVAX在降低中度至重度ETEC发作的发生率方面最为有效。因此，对于疗效试验结果，有必要将患者分为中度至重度疾病和轻度疾病。目前不存在针对ETEC的严重程度分级标准。为了制定该分级标准，PATH召集了一个国际专家委员会举行为期两天的会议，以制定诊断分级标准的策略。研讨会首先进行了四个报告。第一个报告介绍了现有的分级标准、项目选择以及与验证、可靠性和易用性相关的问题。其他三个报告详细介绍了以下已发表的评分：DHAKA评分，已验证可用于寻求腹泻治疗的孟加拉国儿童；改良的Vesikari评分，用于评估北美腹泻门诊儿童；以及为秘鲁腹泻儿童的被动病例监测开发的社区腹泻评估（CODA）评分。在报告和讨论之后，委员会提出了几项建议，包括：修改现有评分以使其以ETEC为中心；根据脱水的客观指标（即补液后儿童体重的变化百分比）评估评分系统；在评分中增加一个项目，测量ETEC对生长发育迟缓的影响。委员会还讨论了使用现有数据集评估评分，但担心如果研究人员使用与评分规定不同的程序对患者进行分类，结果将难以解释。委员会成员建议进行新的数据收集，并建议在撒哈拉以南非洲进行研究。研究结果将提交同行评审并提交给监管机构。
